Levosimendan, which is the (−)-enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, and the method for its preparation is described in EP 565546 B1. Levosimendan is potent in the treatment of heart failure and has significant calcium dependent binding to troponin. Levosimendan is represented by the formula:

The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 1061-1066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S63-S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. The use of levosimendan in the treatment of pulmonary hypertension is described in WO 99/66912. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients.
Septic shock (also known as sepsis) is the leading cause of morbidity and mortality in the intensive care units. Despite increased knowledge about the pathophysiology underlying the clinical symptoms mortality remains high and has not decreased substantially over the last decades.
There are several causes of septic shock including bacterial, fungal and viral infections as well as non-invasive stimuli such as multiple trauma, severe burns, organ transplantations and pancreatitis. The fatal outcome of septic shock has recently been linked to the systemic release of substantial amounts of various cytokines in the body.
Septic shock requires prompt treatment since the patient's condition often deteriorates rapidly. Symptoms of septic shock include fever, hypothermia, falling blood pressure, rapid breathing, rapid heartbeat, skin lesions and leakage of plasma proteins into the tissues, metabolic acidosis and elevated plasma lactate. Septic shock is particularly characterised by maldistribution of blood flow and disturbances in tissue oxygen in various organs of the body. Distribution of blood flow may become heterogenous with subsequent under- and overperfusion of various tissues. These disturbances have been noted both at the macro- as well as at the microcirculatory level. Septic patient usually die as a result of poor tissue perfusion and injury followed by multiple organ failure.
One of the organs in which the disturbances in nutritive flow is especially important is the gut. The importance of preserved of splanchnic blood flow in various shock conditions, including septic shock, has been largely emphasized in the literature. Reductions in splanchnic blood flow have been a suggested contributor to the development of multiple organ failure as well as maintenance of sepsis by translocation of gut derived bacteria over a hyperpermeable gut wall.
Current therapeutic strategies in sepsis include antibiotics, in certain cases surgical intervention, blood volume replacement as well as inotropic support to the failing circulation. However, the current therapy has not proven to be successful. Insufficient response to intropic drugs in terms of cardiac output is not uncommon. Also the distribution of blood flow to various organs may become negatively affected. For example, splanchnic blood flow is not increased in spite of increased cardiac output. Thus, an improved method for treating septic shock would be of great value.